Determining the Optimal Adenosine Provocation Test (impact)

• ClinicalTrials.gov Identifier: NCT01610921
• Recruitment Status: Completed
• First Posted: June 4, 2012
• Last Update Posted: July 11, 2014
• Sponsor: University Medical Center Groningen
• Collaborator: Chiesi Farmaceutici S.p.A.
• Information provided by (Responsible Party): E. van der Wiel, University Medical Center Groningen

Study Description

Brief Summary:

Asthma is a frequently occurring inflammatory lung disease that affects the whole bronchial tree including the small airways (<2mm). Since the introduction of the solution hydrofluoroalkane (HFA) technology it is possible to generate medication with small particles of approximately 1-2 μm, and therefore to reach the small airways. However, at this moment the investigators have no reliable instruments to identify the asthmatic subjects who particularly benefit from treatment with inhaled small particles. Recently the investigators research group investigated whether provocation with small and large particles AMP is able to identify responders and non-responders to treatment with small and large particles of inhaled corticosteroids. This provocation technique gave promising results but needs further optimization.

The aim of this study is to determine the optimal particle size of dry powder adenosine to assess small airway involvement in asthma. Secondary, to provide insight in the associations between the standard test, executed with nebulized AMP, and the new test, executed with dry powder Adenosine.

Condition or disease	Intervention/treatment	Phase
Asthma	Other: Bronchial provocation test	Not Applicable

Detailed Description:

This is a cross-over study. The study population consists of 10 non-smoking asthma patients in the age of 18-65 years who have a PC20 metacholine value ≤4.9mg/ml.

Participating subjects perform 6 provocation tests in randomized order: one test with nebulized methacholine, one test with nebulized AMP, four times dry powder adenosine provocation test. (small particles with inhaled with a slow flow, small particles inhaled with a fast flow, large particles inhaled with a slow flow, large particles inhaled with a fast flow)

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Intervention Model: Single Group Assignment
• Masking: Single (Participant)
• Primary Purpose: Diagnostic
• Official Title: Determining the Optimal Dry Powder Adenosine Provocation Test to Assess Small Airways Disease
• Study Start Date: February 2012
• Actual Primary Completion Date: October 2013
• Actual Study Completion Date: May 2014

Arms and Interventions

Arm

Intervention/treatment

Experimental: bronchial provocationtest; Provocation tests with adenosine dry powder and nebulized AMP (adenosine-5'monophosphate). The AMP provocation test is a standard test and consists of 14 doubling concentrations in a range of 0.04mg/ml to 320mg/ml. The aerosols will be inhaled during tidal breathing for 2 minutes. The dry powder adenosine also consists of 14 doubling steps with doses in a range of 0.01mg to 20mg.

Other: Bronchial provocation test; Provocation tests with adenosine dry powder and nebulized AMP (adenosine-5'monophosphate). The AMP provocation test is a standard test and consists of 14 doubling concentrations in a range of 0.04mg/ml to 320mg/ml. The aerosols will be inhaled during tidal breathing for 2 minutes. The dry powder adenosine also consists of 14 doubling steps with doses in a range of 0.01mg to 20mg.; Other Names: bronchial challenge test; AMP test; adenosine bronchial provocation

Outcome Measures

Primary Outcome Measures :

1. The small airway reaction to provocation with adenosine, reflected by the IOS parameter R5-R20 [ Time Frame: Small airway reaction is measured during each provocation test. The Visits will take place in a period of 6 weeks. ]
   The R5-R20 is measured with the IOS. This a method to determine the resistance of the small airways. The R5-R20 is measured during each provocation test after each provocative step.

Secondary Outcome Measures :

1. The total airway reaction to provocation with adenosine, reflected by the decline in FEV1 (PD20/ PC20 values) [ Time Frame: Lung function is measured during each provocation test. All visits take place in a period of 6 weeks. ]
   We want to compare the different PD20/PC20 values of the three dry powder adenosine provocation test and with the nebulized AMP provocation test. The lung function is measured after each provocative step to determine the point of 20% decline in FEV1. The provocation test is ended after the last step or is ended prematurely when there is a 20% fall of FEV1 compared to baseline

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• A doctor's diagnosis of asthma
• Age: 18-65 years
• PC20 AMP < 320 mg/ml
• Non-smoker
• Steroid naive or steroids have been stopped 4 weeks before entry into the baseline period

Exclusion Criteria:

• Recent exacerbation asthma (<2 months) or upper respiration tract infection (<2 weeks)
• Severe airway obstruction at baseline, FEV1pred< 50% or < 1.2L
• Diagnosis of COPD or any other pulmonary disease that could influence the study results as judged by the investigator
• Pregnancy or lactating women. (i.e. women of childbearing potential who do not use adequate anticonception as judged by the investigator).

Contacts and Locations

Locations

Netherlands

University Medical Center Groningen

Groningen, Netherlands, 9700 RB

University Medical Center Groningen

Groningen, Netherlands, 9700RB

Sponsors and Collaborators

University Medical Center Groningen

Chiesi Farmaceutici S.p.A.

Investigators

• Study Chair: Nick ten Hacken, MD, Phd; University Medical Center Groningen

More Information

• Responsible Party: E. van der Wiel, E. van der Wiel, MD, University Medical Center Groningen
• ClinicalTrials.gov Identifier: NCT01610921 History of Changes
• Other Study ID Numbers: NL 37702.042.12
• First Posted: June 4, 2012
• Last Update Posted: July 11, 2014
• Last Verified: July 2014

Keywords provided by E. van der Wiel, University Medical Center Groningen:

asthma; small airways disease; inflammation; provocation; adenosine

Additional relevant MeSH terms:

Adenosine; Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Vasodilator Agents; Purinergic P1 Receptor Agonists; Purinergic Agonists; Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action